When the blood flow through the cerebral artery or coronary artery is reduced below a threshold value e.g., by the blocking action of thrombosis or arteriosclerosis, the resulting ischemia damages cerebral nerve or cardiac cells, leading to brain or myocardial infarction due to cell death. Brain ischemia is a common symptom observed in cardiac arrest and ischemic stroke and gives rise to an intractable damage to the cerebral neurons, which leads to disability, comatose, or even death.
Pathophysiological mechanisms involved in central nervous system diseases are diverse and complex, but it has been found that reactive oxygen species (ROS) such as free radicals play an important role in central nervous system diseases, e.g., ischemic stroke, Alzheimer's disease and Parkinson's disease. Namely, it has been proposed that various kinds of ROS generated by oxidative stress induce damage to certain nerve cells in acute and chronic degenerative neuronal diseases. Recently, it has been reported that brain damage by ischemic stroke is caused by free radicals generated by ischemia and reperfusion (Koroshetz & Moskowitz, Trends Neurosci. 17:227, 1996).
Free radicals are also responsible for the loss of certain nerve cells observed in Alzheimer's disease. One of the representative clinical manifestations of Alzheimer's disease is senile plaques formed through aggregation of beta-amyloid (Aβ) protein. The aggregated beta-amyloid protein causes hydrogen peroxide to accumulate in nerve cells, which leads to oxidative and peroxidative reactions. Further, these reactions promote the generation of nitric oxide, and the nitric oxide thus generated reacts with a superoxide anion radical to form peroxynitrite with very strong reactivity, which results in increasing radical toxicity.
Likewise, the generation of hydroxyl radical, a strong neurotoxic mediator, by oxidative stress is believed to lead to Parkinson's disease (Ebadi et al., Prog. Neurobiol. 48:1, 1996). Furthermore, it has been suggested that ROS play an important role in excitotoxic neuronal cell death that is caused by glutamate excessively released in acute brain damage and chronic neurodegenerative diseases (Choi, Neuron 1:623, 1988).
Thus, ROS generated by the oxidative stress is directly or indirectly involved in various acute and neudegenerative diseases, e.g., brain ischemia, Alzheimer's disease, Parkinson's disease, and therefore, anti-oxidative substances are being actively investigated for the prevention and treatment of such nerve diseases.
The present inventors have endeavored to find a naturally occurring substance with anti-oxidative activity, and found that an extract of Opuntia ficus-indica (Linné) Mill has significantly strong anti-oxidative activity for protecting nerve cells.
Opuntica ficus-indica has been widely used as a folk remedy for treating burn, edema, indigestion and bronchial asthma, and it has been known that an ethanol extract of Opuntica ficus-indica fruit and stem shows various efficacies for protecting gastric mucosa, lower blood glucose levels and enhance immunity by analgesic and anti-inflammatory actions (Trejo-Gonzalez et al., J. Ethnopharmacol. 55:27-33, 1996; Ahn, Illustrated book of Korean medical herbs Kyohaksa, 497, 1998; Galati et al., J. Ethnopharmacol. 76:1-9, 2001). Recently, it has been also reported that opuntica ficus-indica inhibits tyrosinase which is involved in melanin synthesis (Lee N. H. et al., J. Pharmacognosy 31:412, 2000).
However, there is no report that an ethyl acetate extract of the stem, fruit or processed fruit of Opuntia ficus-indica or a compound isolated therefrom shows anti-oxidative activity for protecting nerve cells, and accordingly, the present invention discloses for the first time that such an extract can be effectively used for preventing and treating chronic nerve diseases such as ischemic stroke and Alzheimer's disease, and cardiac ischemia such as myocardial infarction.